Spironolactone solubility

Drugs in Class II have low aqueous solubility (but high membrane permeability), and any factor affecting dissolution rate would be expected to have an impact on the absorption of such compounds. Factors that are noted in Fig. 11, such as fluid pH, volume and viscosity, and bile secretion (especially in response to fatty foods), might be expected to play a role in dissolution rate and thereby affect absorption. Compounds that fall into this class include carbamazepine, cyclosporin, digoxin, griseofulvin, and spironolactone. Food would be expected to exert a potentially significant affect on... 

D. O. Thompson, and J. P. Mannermaa. Intestinal safety of water-soluble beta-cyclodextrins in paediatric oral solutions of spironolactone effects on human intestinal epithelial Caco-2 cells,... 

Florence, A.T. and Salole, E.G. (1976). Changes in crystallinity and solubility on comminution of digoxin and observations on spironolactone and estradLdpharm. Pharmacol., 28 637-642. 

The following solubility values have been reported for spironolactone in different solvents at room temperature (25°C) [10] ... 

Because of its low aqueous solubility, spironolactone has not been formulated for intravenous administration [72]. The oral absorption of spironolactone is improved by using micronized drug, or through the use of inclusion complexes of spironolactone with cyclodextrins. 

Other approaches already realized include the development of a simple and rapid method for spironolactone determination based on the quenching of the fluorescence of CdSe quantum dots by the analyte52 or the determination of anthracene with a detection limit of 1.6 x 10-8 M based on the quenching effect of this polycyclic aromatic hydrocarbon on water-soluble CdSe/ZnS quantum dots, prepared via a simple sonochemical procedure using (3-cyclodextrin ((3-CD) as surface coating agent.53... 

Eq. 21 assumes that each cosolvent interacts independently. Of course this is not always the case. In fact the data of Pramar and Das Gupta show a synergistic affect for the solubilization of the nonpolar solute, spironolactone. In addition, the use of one cosolvent can be used to increase the solubility of a partially miscible cosolvent in water. The facilitated cosolvency effect of multiple species in water has been shown by Gupta et al. " and Riley. " ... 

Fig. 10 Ternary cosolvent systems and resulting solubilization of spironolactone. So represents the solubility of spironolactone in a 10% ethanol/water system. Given in the figure are different concentrations of PEG-400 with varied propylene glycol or glycerin volume fractions. (From Refill ].)...

Fig. 19 Solubility of spironolactone as a function of cyclodextrin and concentration. O, a-cyclodextrin, , P-cyclodextrin, and. A, y-cyclodextrin. (From Ref. " l)...

Seo et have shown the dependence of stability constant and overall solubility upon cyclodextrin ring size for spironolactone. From the data given in Fig. 19, it can be seen that for the relatively large spironolactone molecule (Fig. 9) the stability constant increases with size of the host cavity that is reflected through an increase in the linear slopes. The lowest maximum solubility was obtained with the p-cyclodex-trin, which has the lowest solubility of the three cyclo-dextrins. ... 

Kaukonen AM, Lennemas H, Mannermaa JP. Water-soluble beta-cyclodextrins in paediatric oral solutions of spironolactone preclinical evaluation of spironolactone bioavailability from solutions of beta-cyclodextrin derivatives in rats. ] Pharm Pharmacol 1998 50(6) 611-619. 

This is a water-soluble prodrug and can be administered parenterally (Figure 16.2). It has no intrinsic activity, but it can exert its diuretic activity (as an aldosterone antagonist) because of its interconversion with canrenone. Canrenone is itself the major metabolite of spironolactone. ... 

Spironolactone (17-hydroxy-7 a-mercapto-3-oxo-17 a-pregn-4-ene-21-carboxylic acid), a diuretic steroidal aldosterone agonist, has been obtained into anhydrous polymorphs as well as four solvated crystalline forms [38]. The compound shows variable and incomplete oral absorption due to its poor water solubility and dissolution rate, factors that are compounded by the existence of polymorphism and solvate formation. The two anhydrate forms (Forms I and II) both crystallize in orthorhombic space groups, and the crystallographic data for these are collected in Table 15. The spironolactone system exhibits the classic... 

---